Research Article

Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins

Centre for Healthy Brain Ageing, University of New South Wales, Australia
The University of Adelaide, Adelaide Medical School, Discipline of Psychiatry, Australia
Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Australia
Mathematics and Statistics, Murdoch University, Australia
Brain and Mind Centre, The University of Sydney, Australia
Neuroscience Research Australia, Australia
Queensland Brain Institute, University of Queensland, Australia
University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Australia
University of New South Wales, Australia

Jul 22, 2020

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Abstract

The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h²=0.28-0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

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https://academic.oup.com/nar/article/47/D1/D529/5204333

Article and author information

Author details

Matthew WK Wong

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Anbupalam Thalamuthu

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Nady Braidy

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Karen A Mather

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Yue Liu

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Liliana Ciobanu

Adelaide Medical School, The University of Adelaide, Adelaide Medical School, Discipline of Psychiatry, Adelaide, Australia

Competing interests
The authors declare that no competing interests exist.
Bernhardt T Baune

Department of Psychiatry, Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Nicola J Armstrong

Mathematics and Statistics, Mathematics and Statistics, Murdoch University, Perth, Australia

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4477-293X
John Kwok

Brain and Mind Centre, Brain and Mind Centre, The University of Sydney, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Peter Schofield

Faculty of Medicine, Neuroscience Research Australia, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Margaret J Wright

Queensland Brain Institute, Queensland Brain Institute, University of Queensland, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7133-4970
David Ames

Academic Unit for Psychiatry of Old Age, University of Melbourne Academic Unit for Psychiatry of Old Age, St George's Hospital, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Russell Pickford

Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Teresa Lee

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Anne Poljak

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Perminder S Sachdev

School of Psychiatry, Faculty of Medicine, Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

For correspondence
p.sachdev@unsw.edu.au

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9595-3220

Funding

National Health and Medical Research Council

Nady Braidy
Perminder S Sachdev

Australian Research Council

Nady Braidy

Rebecca L. Cooper Medical Research Foundation

Nady Braidy
Anne Poljak
Perminder S Sachdev

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: OATS was approved by the Ethics Committees of the University of New South Wales and the South Eastern Sydney Local Health District (ethics approval HC17414). All work involving human participants was performed in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Informed consent was obtained from all participants and/or guardians.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.